Abstract The survival of children with Down syndrome (DS), one of the most common birth defects, has improved markedly over the past few decades. However, substantial racial/ethnic disparities in survival have been identified. Children with DS often have co-occurring birth defects and other health and developmental comorbidities that affect the quality of their lives and influence public health programming. Longitudinal studies using population-based data are needed to understand the risk and preventive factors associated with racial/ethnic and other disparities in survival of and health and developmental comorbidities among children with DS. The proposed research builds upon and extends the ongoing PELL Down syndrome Project (PDSP), which uses the Massachusetts (MA) population-based Pregnancy to Early Life Longitudinal (PELL) data system to examine prevalence of and disparities in infant morbidity and mortality, hospital service utilization, and associated costs, among children with DS in MA from 2001-2005 overall and among four DS sub-groups: DS only, DS + congenital heart defects (CHD), DS + CHD + other major non-cardiac birth defects (OMBD), and DS+OMBD. The proposed study expands the PDSP database by adding the 2006 and 2007 birth cohorts and data on newborn hearing, extends the longitudinal follow-up period through 3 years of age, and proposes new novel analyses to examine and identify potential reasons for racial/ethnic and other disparities among children with DS for the following outcomes: 1) health comorbidities to ages 1 and 3 years;2) survival to ages 1 and 3; and 3) developmental comorbidities to age 3. Using the PELL system's unique longitudinal linkages among multiple health and human service data sets, the proposed project will generate novel individual, contextual, and programmatic/health service level data to examine disparities in comorbidities and survival among children with DS. The study will develop enhanced measures of health comorbidities, sociodemographic characteristics, and health service utilization. National Death Index data will strengthen the survival analysis. Extensive information from Early Intervention (EI) will be used to more fully characterize developmental attainment, EI service usage, and Autism Spectrum Disorder co-occurrence. This project brings together a large, experienced research team with a wide range of knowledge and skills. The three study aims and sub-aims will be assessed using bivariate, stratified multivariate, and multi-level modeling. Study results will provide new, critical information that can influence DS programs and policies to improve the health, survival and developmental trajectories of children with DS, their families, and their communities.